{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:52:37Z","timestamp":1791456757573,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013669","name":"Ionis Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013669","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>MECP2<\/jats:italic>\n                    Duplication Syndrome (MDS) is a rare, X\u2010linked neurodevelopmental disorder typically affecting males. Females with MDS have been reported and are compiled here. We conducted a systematic review (PROSPERO CRD420250652426) of PubMed, EMBASE, and Google Scholar extracting individual participant data. Inclusion required confirmed full\n                    <jats:italic>MECP2<\/jats:italic>\n                    gene duplication and evidence of ID (IQ\u2009&lt;\u200975 or significant deficits in adaptive functioning). Affected females were compared with a published male MDS dataset, stratified by genetic variant. From 590 full\u2010texts, 41 unique female records were included. Tandem duplications were most frequent (59%), followed by unbalanced autosomal translocations (32%), other terminal duplications (7.3%), and one triplication. Most tandem duplication females exhibited skewed X\u2010inactivation (14\/18 reports) and presented with mild\u2010to\u2010moderate developmental delay, partially retained speech and ambulation (all but one report), and fewer neurological\/systemic manifestations relative to male counterparts. Females with unbalanced translocations or other terminal duplications had severe ID, absent speech (5\/9 reports), and severe epilepsy (8\/16 reports included drug\u2010resistant epilepsy). Features included respiratory infections (12\/14), feeding problems (8\/11), microcephaly (10\/14), and shortened survival. Affected females show genotype\u2010dependent severity: tandem duplications were associated with broader, generally less severe phenotypes and variable epilepsy expression, whereas severe translocation\/terminal duplication females may resemble male MDS.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70318","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:12:51Z","timestamp":1791454371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic Review of Females With Intellectual Disability and\n                    <scp>\n                      <i>MECP2<\/i>\n                    <\/scp>\n                    Duplication"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5687-6791","authenticated-orcid":false,"given":"Paul","family":"Malik","sequence":"first","affiliation":[{"name":"Ionis Pharmaceuticals  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5788-0270","authenticated-orcid":false,"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Section of Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-3153","authenticated-orcid":false,"given":"Antonio F.","family":"Martinez\u2010Monseny","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de Deu  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-1622","authenticated-orcid":false,"given":"Mar","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hospital Sant Joan de D\u00e9u, Institut de Recerca Sant Joan de D\u00e9u, CIBERER  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-9307","authenticated-orcid":false,"given":"Judith","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Laboratory Service\u2010 Genomics Unit Hospital Sant Joan de D\u00e9u, Institut de Recerca Sant Joan de Deu, CIBERER  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-5402","authenticated-orcid":false,"given":"Sarika U.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6772-9663","authenticated-orcid":false,"given":"Steven T.","family":"Lee","sequence":"additional","affiliation":[{"name":"Section of Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Feyma","sequence":"additional","affiliation":[{"name":"Gillette Children's Hospital  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3551-1201","authenticated-orcid":false,"given":"Paola","family":"Mian","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8183-9697","authenticated-orcid":false,"given":"Christine","family":"Coquery","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2022.05.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2009.01363.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320460212"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12060860"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010015\u20100129\u20105"},{"issue":"5","key":"e_1_2_10_7_1","first-page":"300","article-title":"Do Novo Trisomy Xq28\u2010Qter Detected by Subtelomeric FISH Screening","volume":"73","author":"Bialer M. 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